The aims of the HASD Neuropathology Core D and Brain Tissue Bank are: 1. To make neuropathologic diagnoses on all new brain accessions from HASD research subjects using standard diagnostic criteria where possible. Alzheimer's disease lesion severity will be quantified using the staging scheme of Braak and Braak (1991 and 2006). The neuropathologic diagnosis of Alzheimer's disease (AD) is based on NIA-Reagan Institute (1997), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD; 1997), and Khachaturian (1985) criteria. The severity of Lewy body pathology will be assessed using the criteria of Braak et a/. (2003) and the diagnosis of dementia with Lewy bodies will be determined using the criteria of McKeith et a/. (2005). Neuropathologic diagnostic criteria for frontotemporal lobar degeneration will be determined using the consensus criteria of Cairns et a/. (2007). Other criteria will be applied where appropriate. 2. To perform brain autopsies and to collect, store at -80C, and distribute frozen and formalin fixed, paraffin wax-embedded tissues to support HASD projects and investigators and outside collaborations that complement in-house research. 3. To maintain a neuropathology computerized database in concert with the Biostatistics and Clinical Cores and the Washington University Neuroscience Blueprint Interdisciplinary Center Core (P30-NS057105). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi-quantitative morphometric data, neuropathology reports (in collaboration with Dr Schmidt, Chair, Division of Neuropathology), bibliographic information, and data relevant to Core tissue banking activities. In addition, neuropathology data will be transferred, after Biostatistics Core quality control and validation, to the National Alzheimer Coordinating Center (NACC), Washington University, Seattle, WA (U01-AG016976). 4. To establish Consensus Criteria for the Neuropathologic Diagnosis of Early AD. A major achievement of this project will be the establishment of new pathological diagnostic criteria for the earliest brain changes of AD. Using immunohistochemical and stereological methods the early changes associated with disease will be quantified and consensus criteria developed. Together, this project and the supporting cores will define the earliest pathological and biochemical stages of AD in comparison with healthy brain aging. To accomplish these aims, Core D will work closely with other Cores, Core leaders and Project leaders. There is no budgetary or scientific overlap with the activities of the Neuropathology Core and Brain Tissue Bank of the Washington University Alzheimer's Disease Research Center (ADRC).